Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-49658 Wissenschaftlicher Artikel Send, Tabea; Bardtke, S.; Gilles, M.; Wolf, I. A. C.; Sütterlin, Marc Wolf; Wudy, S. A.; Wang, R.; Laucht, Manfred; Witt, Stephanie H.; Rietschel, Marcella; Streit, Fabian; Deuschle, Michael Prenatal maternal stress is associated with lower cortisol and cortisone levels in the first morning urine of 45-month-old children Prenatal stress (PS) has been related to altered hypothalamic-pituitary-adrenal (HPA) axis activity later in life. So far, studies in children assessing HPA axis functioning have focused on salivary cortisol, reflecting daytime activity. The present work is part of a prospective study and aims to extend knowledge about the association between PS and HPA axis regulation in children. To do so, we investigated cortisol, cortisone, and the ratio cortisone/(cortisone + cortisol) in the first morning urine of 45-month-old children in relation to several measures of maternal stress during pregnancy. Urinary cortisol and cortisone were measured by online turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry. PS was defined as: perceived stress for aim 1 (Perceived Stress Scale; n = 280); presence of self-reported (n = 371) and expert-rated psychopathology for aim 2 (Mini International Neuropsychiatric Interview; n = 281); continuous measures of anxiety and depression for exploratory aim 3 (State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale; n = 280). The ratio cortisone/(cortisone + cortisol) as a global marker for the balance between the enzymes metabolizing cortisol to cortisone and vice versa (11 beta-hydroxysteroid dehydrogenases type 1 and 2; 11 beta-HSD1 and 2) was not associated with any measure of maternal PS (aims 1-3). The present study provides insight into possible programming effects of PS on nocturnal HPA axis activity and a proxy of 11 beta-HSD in a large sample. The results suggest that the nocturnal rate of cortisol production is lower in children exposed to PS, but do not support the hypothesis of divergent 11 beta-HSD activity. Oxford Elsevier 2019 6 Psychoneuroendocrinology 103 219 224 10.1016/j.psyneuen.2019.01.017 Department Psychologie OPUS4-51900 misc Send, T. S.; Gilles, M.; Codd, V.; Wolf, I. A. C.; Bardtke, S.; Streit, Fabian; Strohmaier, Jana; Frank, Josef; Schendel, D.; Sutterlin, M. W.; Denniff, M.; Laucht, Manfred; Samani, N. J.; Deuschle, Michael; Rietschel, Marcella; Witt, Stephanie H. Telomere length in newborns is related to maternal stress during pregnancy Response London Nature Publ. Group 2018 1 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 43 11 2164 2164 10.1038/s41386-018-0079-8 Department Psychologie OPUS4-53853 Wissenschaftlicher Artikel Wolf, Isabell Ann-Cathrin; Gilles, Maria; Peus, Verena; Scharnholz, Barbara; Seibert, Julia; Jennen-Steinmetz, Christine; Krumm, Bertram; Rietschel, Marcella; Deuschle, Michael; Laucht, Manfred Impact of prenatal stress on mother-infant dyadic behavior during the still-face paradigm Background: Mother-infant interaction provides important training for the infant's ability to cope with stress and the development of resilience. Prenatal stress (PS) and its impact on the offspring's development have long been a focus of stress research, with studies highlighting both harmful and beneficial effects. The aim of the current study was to examine the possible influence of both psychological stress and hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy with mother-child dyadic behavior following stress exposure. Methods: The behavior of 164 mother-infant dyads during the still-face situation was filmed at six months postpartum and coded into three dyadic patterns: 1) both positive, 2) infant protesting-mother positive, and 3) infant protesting-mother negative. PS exposure was assessed prenatally according to psychological measures (i.e., psychopathological, perceived and psychosocial PS; n = 164) and HPA axis activity measures (maternal salivary cortisol, i.e., cortisol decline and area under the curve with respect to ground (AUCg); n = 134). Results: Mother-infant dyads in both the high- and low-stress groups showed decreasing positive and increasing negative dyadic behavior in the reunion episode, which is associated with the well-known "still-face" and "carry-over" effect. Furthermore, mother-infant dyads with higher psychosocial PS exhibited significantly more positive dyadic behavior than the low psychosocial PS group in the first play episode, but not in the reunion episode. Similarly, mother-infant dyads with high HPA axis activity (i.e. high AUCg) but steeper diurnal cortisol decline (i.e. cortisol decline) displayed significantly less negative behavior in the reunion episode than dyads with low HPA axis activity. No significant results were found for psychopathological stress and perceived stress. Conclusions: The results suggest a beneficial effect of higher psychosocial PS and higher prenatal maternal HPA axis activity in late gestation, which is in line with "stress inoculation" theories. London BioMed Central 2018 13 Borderline Personality Disorder and Emotion Dysregulation : the official journal of the National Education Alliance for Borderline Personality Disorder (NEA.BPD) and Dachverband Dialektisch Behaviorale Therapie (DDBT) 5 10.1186/s40479-018-0078-8 Department Psychologie OPUS4-53308 Wissenschaftlicher Artikel Witt, Stephanie H.; Frank, Josef; Gilles, Maria; Lang, Maren; Treutlein, Jens; Streit, Fabian; Wolf, Isabell A. C.; Peus, Verena; Scharnholz, Barbara; Send, Tabea S.; Heilmann-Heimbach, Stefanie; Sivalingam, Sugirthan; Dukal, Helene; Strohmaier, Jana; Sütterlin, Marc; Arloth, Janine; Laucht, Manfred; Nöthen, Markus M.; Deuschle, Michael; Rietschel, Marcella Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight. London BMC 2018 10 BMC genomics 19 10.1186/s12864-018-4652-7 Department Psychologie OPUS4-52424 Wissenschaftlicher Artikel Gilles, Maria; Otto, Henrike; Wolf, Isabell A. C.; Scharnholz, Barbara; Peus, Verena; Schredl, Michael; Suetterlin, Marc W.; Witt, Stephanie H.; Rietschel, Marcella; Laucht, Manfred; Deuschle, Michael Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress measures at birth Background: Prenatal maternal stress might be a risk for the developing fetus and may have long-lasting effects on child and adult vulnerability to somatic and psychiatric disease. Over-exposure of the unborn to excess glucocorticoids and subsequent alteration of fetal development is hypothesized to be one of the key mechanisms linking prenatal stress with negative child outcome. Methods: In this prospective longitudinal study, mothers-to-be (n = 405) in late pregnancy (36.8 +/- 1.9 weeks of gestational age) and their singleton neonates were studied. We investigated the impact of different prenatal stress indices derived from six stress variables (perceived stress, specific prenatal worries, negative life events, symptoms of depression, trait anxiety, neuroticism) and diurnal maternal saliva cortisol secretion on gestational age and anthropometric measures at birth. Oxford Elsevier 2018 10 Psychoneuroendocrinology 94 152 161 10.1016/j.psyneuen.2018.04.022 Department Psychologie OPUS4-50082 Wissenschaftlicher Artikel Send, Tabea Sarah; Bardtke, Svenja; Gilles, Maria; Wolf, Isabella Germaine; Sütterlin, Marc W.; Kirschbaum, Clemens; Laucht, Manfred; Witt, Stephanie H.; Rietschel, Marcella; Streit, Fabian; Deuschle, Michael Stress reactivity in preschool-aged children Prenatal maternal stress is an established risk factor for somatic and psychological health of the offspring. A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in offspring has been suggested as an important mechanism. However, the impact of prenatal stress on stress reactivity in preschool-aged children is not yet well understood. This is partly due to the fact that for this age group there is no stress test as well established as for older children and adults. In the present work a previously published stress test (Kryski et al., 2011) was evaluated in a large sample of 45-month-old children (n = 339). Furthermore, the relation between measures of prenatal maternal stress and cortisol reactivity was investigated. Prenatal stress was defined as psychopathology (self-report available for n = 339; expert-rating available for a subsample of n = 246) and perceived stress (n = 244) during pregnancy. The stress paradigm elicited significant increases in salivary cortisol 30 and 40 min after the test, and 60.8% of the children were classified as responders. Lower cortisol levels after the stress test were observed in the group of children with prenatal stress defined as maternal psychopathology (both self-reported and expert-rated). Maternal perceived stress as a continuous measure was not significantly associated with cortisol levels. However, when comparing children in the highest quartile of maternal perceived stress to all other children, significantly lower cortisol values were observed in the prenatally stressed group. The present study confirms the paradigm by Kryski et al. as an effective stress test for preschool-aged children. Moreover, it provides further evidence that prenatal stress impacts HPA axis reactivity. Future studies should target the timing, nature, and intensity of prenatal stressors and their effect on the stress response in offspring at different developmental stages. Oxford Elsevier 2018 9 Psychoneuroendocrinology 101 223 231 10.1016/j.psyneuen.2018.11.002 Department Psychologie OPUS4-46231 Wissenschaftlicher Artikel Send, Tabea Sarah; Gilles, Maria; Codd, Veryan; Wolf, Isabell; Bardtke, Svenja; Streit, Fabian; Strohmaier, Jana; Frank, Josef; Schendel, Darja; Suetterlin, Mark W.; Denniff, Matthew; Laucht, Manfred; Samani, Nilesh J.; Deuschle, Michael; Rietschel, Marcella; Witt, Stephanie H. Telomere Length in Newborns is Related to Maternal Stress During Pregnancy Telomere length (TL) is a marker of biological aging, and numerous studies have shown associations between TL and somatic or psychiatric disorders. Research also indicates an association between maternal stress during pregnancy and TL in the offspring. The present study investigated possible associations between TL and: (1) maternal perceived stress during pregnancy; (2) a maternal lifetime history of psychiatric disorder (lifetime PD); and (3) paternal age. TL was analyzed in 319 newborns and 318 mothers from a predominantly Caucasian sample (n= 273 Caucasian newborns and n= 274 Caucasian mothers). Two key findings were observed. First, maternal perceived stress during pregnancy was associated with shorter telomeres in newborns but not with maternal TL. Second, maternal lifetime PD was associated with shorter maternal telomeres, but not with TL in newborns. Paternal age was not associated with TL in newborns. The finding that maternal stress during pregnancy is associated with shorter telomeres in newborns supports the results of smaller previous studies. The fact that a relation between maternal prenatal stress and TL was observed in the offspring but not in mothers may be attributable to a high vulnerability to stress during intrauterine development of a maturing organism. To our knowledge, this is the largest study to date to show that maternal stress during pregnancy but not maternal lifetime PD is associated with shorter telomeres in the offspring. London Nature Publ. Group 2017 7 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 42 2407 2413 10.1038/npp.2017.73 OPUS4-45569 Wissenschaftlicher Artikel Holz, Nathalie; Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Baumeister, Sarah; Hohmann, Sarah; Jennen-Steinmetz, Christine; Wolf, Isabella; Rietschel, Marcella; Witt, Stephanie H.; Plichta, Michael M.; Meyer-Lindenberg, Andreas; Schmidt, Martin H.; Esser, Günter; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOAx CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders. Cary Oxford Univ. Press 2016 11 Cerebral cortex 26 904 914 10.1093/cercor/bhu249 Department Psychologie OPUS4-45115 Wissenschaftlicher Artikel Hohmann, Sarah; Zohsel, Katrin; Buchmann, Arlette F.; Blomeyer, Dorothea; Holz, Nathalie; Boecker-Schlier, Regina; Jennen-Steinmetz, Christine; Rietschel, Marcella; Witt, Stephanie H.; Schmidt, Martin H.; Esser, Günter; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Hohm, Erika; Laucht, Manfred Interacting effect of MAOA genotype and maternal prenatal smoking on aggressive behavior in young adulthood Findings on the etiology of aggressive behavior have provided evidence for an effect both of genetic factors, such as variation in the monoamine oxidase A (MAOA) gene, and adverse environmental factors. Recent studies have supported the existence of gene × environment interactions, with early experiences playing a key role. In the present study, the effects of prenatal nicotine exposure, MAOA genotype and their interaction on aggressive behavior during young adulthood were examined. In a sample of 272 young adults (129 males, 143 females) from an epidemiological cohort study, smoking during pregnancy was measured with a standardized parent interview at the offspring's age of 3 months. Aggressive behavior was assessed between the ages of 19 and 25 years using the Young Adult Self-Report. DNA was genotyped for the MAOA 5′ untranslated region variable number of tandem repeats polymorphism (VNTR). Results revealed a significant interaction between MAOA and smoking during pregnancy, indicating higher levels of aggressive behavior in young adults carrying the MAOA low-expressing genotype who had experienced prenatal nicotine exposure (n = 8, p = .025). In contrast, in carriers of the MAOA high-expressing genotype, maternal smoking during pregnancy had no effect on aggressive behavior during young adulthood (n = 20, p = .145). This study extends earlier findings demonstrating an interaction between MAOA genotype and prenatal nicotine exposure on aggressive behavior into young adulthood. The results point to the long-term adverse effects of smoking during pregnancy on the offspring's mental health, possibly underlining the importance of smoking cessation during pregnancy. According to the nature of the study (particularly sample size and power), analyses are exploratory and results need to be interpreted cautiously. Wien Springer 2016 10 Journal of neural transmission 123 885 894 10.1007/s00702-016-1582-x Department Psychologie OPUS4-45339 Wissenschaftlicher Artikel Boecker-Schlier, Regina; Holz, Nathalie E.; Buchmann, Arlette F.; Blomeyer, Dorothea; Plichta, Michael M.; Jennen-Steinmetz, Christine; Wolf, Isabella; Baumeister, Sarah; Treutleind, Jens; Rietschel, Marcella; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood Background: Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G x E) on neuronal activity during reward processing. Methods: 168 healthy young adults from a prospective study conducted over 25 years participated in amonetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. Results: At reward delivery, a G x E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. Conclusions: These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G x E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. (C) 2016 Elsevier Inc. All rights reserved. San Diego Elsevier 2016 15 NeuroImage : a journal of brain function 132 556 570 10.1016/j.neuroimage.2016.02.006